It is proposed to study the effects of some cyclic AMP analogues on renal function and metabolism. Using an isolated perfused rat kidney, the capacity of these analogues to (1) penetrate renal tissue, (2) alter protein kinase activity and distribution, (3) alter cyclic AMP-phosphodiesterase activity and cyclic AMP levels, (4) be metabolized to other purine analogues, (5) alter levels of purines in kidney and extracellular fluids, (6) regulate renal gluconeogenesis, and (7) regulate the renal reabsorption of water and ions (Ca, Na, K, phosphate, bicarbonate). Analogues to be tested include substitutions at or on the N1, N6, C8, O2' and on the phosphate moiety (5') of cyclic AMP. High pressure liquid chromatography will be used to quantitate analogues and their metabolites. These studies will clarify which renal functions are regulated by cyclic AMP, which functions are regulated by metabolism of exogenous cyclic AMP or analogue beyond cleavage at the 3'-phosphate ester bond and elucidate the molecular interaction between protein kinase and cyclic AMP.